This subproject is one of many research subprojects utilizing the resources provided by a Center grant funded by NIH/NCRR. The subproject and investigator (PI) may have received primary funding from another NIH source, and thus could be represented in other CRISP entries. The institution listed is for the Center, which is not necessarily the institution for the investigator. Our goal is to develop new medical therapies to reduce heavy menstrual bleeding in women. Menstrual bleeding is triggered by an acute decrease in systemic progesterone. Our hypothesis is that progesterone withdrawal triggers local inflammation coupled with the ingress of leukocytes (neutrophils and macrophages), which results in loss of blood vessel integrity, epithelial necrosis and sloughing of the upper layers of endometrium. Leukocyte infiltration is mediated by the local expression of small secreted proteins (chemokines) including interleukin 8 (IL-8;CXCL8) and monocyte chemoattractant protein (MCP-1;CCL-2). Antagonists that block the receptors for IL8 and MCP-1 (CXCR2 and CCR2b) have been developed.Rhesus macaques are menstruating nonhuman primates with menstrual cycles that are very similar to those of women and can provide a model for testing AZ01 and AZ02 on menstrual blood loss (MBL). Our Aims are as follows: Aim 1 is to validate new methods for the measurement of menstrual blood loss in rhesus macaques; Aim 2 is to test the effects of AZ01 and AZ02 on menstrual bleeding in rhesus macaques. Specific Aim 1 is completed and results will be presented in 2010.